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Background Perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to reduce inflammatory response in relation to surgery. Inflammation may promote recurrence of cancer, thus inhibition by use of NSAIDs could reduce recurrence after surgery. Objective The aim of this study was to examine the association between perioperative use of NSAIDs and cancer recurrence, as well as disease-free survival (DFS) and mortality after colorectal cancer surgery. Methods This was a cohort study based on data from a prospective clinical database, electronic medical records, and nationwide registers, and included patients from six major colorectal centers in Denmark. The primary outcome was cancer recurrence, while secondary outcomes included 5-year mortality and DFS. Results Overall, 2308 patients undergoing colorectal cancer surgery between 1 January 2006 and 31 December 2009 were included. A total of 909 patients received at least 2 days of treatment with NSAIDs, of whom 702 (77.2%) received ibuprofen and 204 (22.4%) received diclofenac. Cox regression analysis adjusting for NSAIDs resulted in decreased recurrence risk (adjusted hazard ratio [HR adjusted ] 0.84, 95% confidence interval [CI] 0.72–0.99; p  = 0.042). Competing risk analysis confirmed the finding, with an HR adjusted of 0.76 (95% CI 0.60–0.97; p  = 0.026). There was no significant effect on mortality or DFS. Sensitivity analysis of the effect of ibuprofen reported an HR adjusted of 0.83 (95% CI 0.70–1.00; p  = 0.047). In restricted analyses of localized disease only (Union for International Cancer Control [UICC] I–II) and elective surgery only, no effect was found (localized: HR adjusted 0.81, 95% CI 0.62–1.06, p  = 0.12; elective: HR adjusted 0.85, 95% CI 0.72–1.01, p  = 0.063). Conclusions Perioperative use of NSAIDs was associated with a reduced risk of cancer recurrence after resection for colorectal cancer. No effect on 5-year mortality or DFS was found.

BackgroundUnrecognized organ hypoperfusion may cause major postoperative complications with detrimental effects for the patient. The use of Indocyanine Green (ICG) to detect organ hypoperfusion is emerging but the optimal methodology is still uncertain. The purpose of this study was to determine the feasibility of real-time continuous quantitative perfusion assessment with Indocyanine Green (ICG) to monitor organ perfusion during minimally invasive surgery using a novel ICG dosing regimen and quantification software.MethodIn this experimental porcine study, twelve subjects were administered a priming dose of ICG, followed by a regimen of high-frequency (1 dose per minute), low-dose bolus injections with weight-adjusted (0.008 mg/kg) ICG allowing for continuous perfusion monitoring. In each pig, one randomly assigned organ of interest [stomach (n = 3), ascending colon (n = 3), rectum (n = 3) and spleen (n = 3)] was investigated with varying camera conditions. Video recording was performed with the 1588 AIM Stryker camera platform and subsequent quantitative analysis of the ICG signal were performed using a research version of a commercially available surgical real-time analysis software.ResultsUsing a high-frequency, low-dose bolus ICG regimen, fluorescence visualization and quantification in abdominal organs were successful in the stomach (3/3), ascending colon (1/3), rectum (2/3), and the spleen (3/3). ICG accumulation in the tissue over time did not affect the quantification process. Considerable variation in fluorescence signal was observed between organs and between the same organ in different subjects. Of the different camera conditions investigated, the highest signal was achieved when the camera was placed 7.5 cm from the target organ.ConclusionThis proof-of-concept study finds that real-time continuous perfusion monitoring in different abdominal organs using ICG is feasible. However, the study also finds a large variation in fluorescence intensity between organs and between the same organ in different subjects while using a fixed weight-adjusted dosing regimen using the same camera setting and placement.

Serrated lesions and polyps (SP) are precursors of up to 30 % of colorectal cancers (CRC) through the serrated pathway. This often entails early BRAF mutations and MLH1 hypermethylation leading to mismatch repair deficient (dMMR) CRC. We investigated predictors of dMMR CRC among patients with co-occurrence of CRC and SP to increase our knowledge on the serrated pathway. We used data from The Danish Pathology Registry and Danish Colorectal Cancer Groups Database from the period 2010–2021 to investigate risk factors for development of dMMR CRC. We used logistic regression models to identify difference in risk factors of developing dMMR CRC in comparison to CRC with proficient MMR (pMMR). We included 3273 patients with a median age of 70.7 years [64.3,76.4] of which 1850 (56.5 %) were male. dMMR CRC was present in 592 patients (18.1 %), with loss of MLH1/PMS2 being most common. The risk of dMMR CRC was significantly higher in females OR 3.47 [2.87;4.20]. When adjusting for age, SP subtype, conventional adenomas (CA), anatomical location and lifestyle factors, female sex remained the strongest predictor OR 2.84 [2.27;3.56]. The presence of sessile serrated lesions with or without dysplasia was related to higher risk OR 1.60 [1.11;2.31] and OR 1.42 [1.11;1.82] respectively, while conventional adenomas constituted a lower risk OR 0.68 [0.55;0.84]. In conclusion we found several predictors of whom female sex had the strongest correlation with dMMR CRC in patients with SP. •Female sex is the strongest predictor for dMMR colorectal cancer in patients with serrated lesions and polyps.•Sessile serrated lesions with and without dysplasia are correlated to at higher risk of dMMR colorectal cancer.•Conventional adenomas are correlated to a lower risk of dMMR colorectal cancer.

The association between pre- and perioperative inflammatory biomarkers, major complications, and survival rates after resection of colorectal cancer (CRC) in older patients is largely unknown. The aim was to investigate age-dependent differences in these associations. Serum CRP, IL-6, and YKL-40 were measured preoperatively and on the first and second day after resection of CRC (stages I–III) in 210 older (≥70 years) and 191 younger patients (<70 years). The results from the complications was presented as an odds ratio (OR, with a 95% confidence interval (CI)) with logistic regression. Results from the mortality rates were presented as a hazard ratio (HR, with a 95% CI) using Cox proportional hazards regression. The preoperative inflammatory biomarkers were higher in the older vs. the younger patients. The risk of complications was increased in older patients with a high preoperative CRP (OR = 1.25, 95% CI 1.03–1.53), IL-6 (OR = 1.57, 95% CI 1.18–2.08), and YKL-40 (OR = 1.66, 95% CI 1.20–2.28), but not in younger patients. Mortality was higher in younger patients with high preoperative YKL-40 (HR = 1.66, 95% CI 1.06–2.60). This was not found in older patients. Elevated preoperative inflammatory biomarkers among older patients were associated with an increased risk of complications, but not mortality. Preoperative inflammatory biomarkers may be useful in assessing the risk of a complicated surgical course in older patients with CRC.

BackgroundPreserving sufficient oxygen supply to the tissue is fundamental for maintaining organ function. However, our ability to identify those at risk and promptly recognize tissue hypoperfusion during abdominal surgery is limited. To address this problem, we aimed to develop a new method of perfusion monitoring that can be used during surgical procedures and aid surgeons’ decision-making.MethodsIn this experimental porcine study, thirteen subjects were randomly assigned one organ of interest [stomach (n = 3), ascending colon (n = 3), rectum (n = 3), and spleen (n = 3)]. After baseline perfusion recordings, using high-frequency, low-dose bolus injections with weight-adjusted (0.008 mg/kg) ICG, organ-supplying arteries were manually and completely occluded leading to hypoperfusion of the target organ. Continuous organ perfusion monitoring was performed throughout the experimental conditions.ResultsAfter manual occlusion of pre-selected organ-supplying arteries, occlusion of the peripheral arterial supply translated in an immediate decrease in oscillation signal in most organs (3/3 ventricle, 3/3 ascending colon, 3/3 rectum, 2/3 spleen). Occlusion of the central arterial supply resulted in a further decrease or complete disappearance of the oscillation curves in the ventricle (3/3), ascending colon (3/3), rectum (3/3), and spleen (1/3).ConclusionContinuous organ-perfusion monitoring using a high-frequency, low-dose ICG bolus regimen can detect organ hypoperfusion in real-time.

Purpose The purpose of this study was to evaluate the concordance between patient-reported performance status (prPS) and surgeon-reported performance status (srPS), and to assess the correlation between srPS and prPS and postoperative complications following elective colorectal cancer surgery. Not all patients are deemed suitable for undergoing a surgical procedure. We aimed to assess whether prPS can aid the surgeons’ decision-making prior to surgery. Methods In this retrospective study, 524 patients undergoing colorectal cancer surgery were included. prPS were collected via questionnaires, while 30-day postoperative complications were obtained from the Danish Colorectal Cancer Group (DCCG) database. To evaluate the agreement between prPS and srPS, linearly weighted kappa statistics were applied. Rank-biserial correlation analysis was used to calculate the correlation between prPS and srPS with postoperative complications. Results In total, there was an approximate 71% concordance between the assessments. Around 17% of the patients rated themselves with a higher PS status than the surgeons, while 13% of the patients rated themselves with a lower PS. Overall postoperative complications, minor surgical complications, and medical complications were all significantly correlated to both srPS and prPS, while only srPS was correlated with major surgical complications. Neither srPS nor prPS were correlated with overall surgical complications (major and minor collapsed). Conclusion The agreement between prPS and srPS is poor and in nearly one-third of the cases, disagreement occurs. Overall, both prPS and srPS were correlated to postoperative complications, with srPS demonstrated a slightly higher correlation.

BackgroundSecuring sufficient blood perfusion to the anastomotic area after low-anterior resection is a crucial factor in preventing anastomotic leakage (AL). Intra-operative indocyanine green fluorescent imaging (ICG-FI) has been suggested as a tool to assess perfusion. However, knowledge of inter-observer variation among surgeons in the interpretation of ICG-FI is sparse. Our primary objective was to evaluate inter-observer variation among surgeons in the interpretation of bowel blood-perfusion assessed visually by ICG-FI. Our secondary objective was to compare the results both from the visual assessment of ICG and from computer-based quantitative analyses of ICG-FI between patients with and without the development of AL. MethodA multicenter study, including patients undergoing robot-assisted low anterior resection with stapled anastomosis. ICG-FI was evaluated visually by the surgeon intra-operatively. Postoperatively, recorded videos were anonymized and exchanged between centers for inter-observer evaluation. Time to visibility (TTV), time to maximum visibility (TMV), and time to wash-out (TWO) were visually assessed. In addition, the ICG-FI video-recordings were analyzed using validated pixel analysis software to quantify blood perfusion.ResultsFifty-five patients were included, and five developed clinical AL. Bland–Altman plots (BA plots) demonstrated wide inter-observer variation for visually assessed fluorescence on all parameters (TTV, TMV, and TWO). Comparing leak-group with no-leak group, we found no significant differences for TTV: Hazard Ratio; HR = 0.82 (CI 0.32; 2.08), TMV: HR = 0.62 (CI 0.24; 1.59), or TWO: HR = 1.11 (CI 0.40; 3.11). In the quantitative pixel analysis, a lower slope of the fluorescence time-curve was found in patients with a subsequent leak: median 0.08 (0.07;0.10) compared with non-leak patients: median 0.13 (0.10;0.17) (p = 0.04).ConclusionThe surgeon’s visual assessment of the ICG-FI demonstrated wide inter-observer variation, there were no differences between patients with and without AL. However, quantitative pixel analysis showed a significant difference between groups.Trial RegistrationClinicalTrials.gov Identifier: NCT04766060.

BackgroundLocal excision of early colon cancers could be an option in selected patients with high risk of complications and no sign of lymph node metastasis (LNM). The primary aim was to assess feasibility in high-risk patients with early colon cancer treated with Combined Endoscopic and Laparoscopic Surgery (CELS).MethodsA non-randomized prospective feasibility study including 25 patients with Performance Status score ≥ 1 and/or American Society of Anesthesiologists score ≥ 3, and clinical Union of International Cancer Control stage-1 colon cancer suitable for CELS resection. The primary outcome was failure of CELS resection, defined as either: Incomplete resection (R1/R2), local recurrence within 3 months, complication related to CELS within 30 days (Clavien–Dindo grade ≥ 3), death within 30 days or death within 90 days due to complications to surgery.ResultsFifteen patients with clinical T1 (cT1) and ten with clinical T2 (cT2) colon cancer and without suspicion of metastases were included. Failure occurred in two patients due to incomplete resections. Histopathological examination classified seven patients as having pT1, nine as pT2, six as pT3 adenocarcinomas, and three as non-invasive tumors. In three patients, the surgical strategy was changed intraoperatively to conventional colectomy due to tumor location or size. Median length of stay was 1 day. Seven patients had completion colectomy performed due to histological high-risk factors. None had LNM.ConclusionsIn selected patients, CELS resection was feasible, and could spare some patients large bowel resection.

Background/Aim: The Danish National Patient Registry (DNPR) provides unique epidemiological insight, but often lacks granular data. We propose a procedure-based definition of cancer status in patients with breast-, lung- and colorectal cancer, which can be applied to administrative health databases. New definitions of cancer status are needed as mortality and morbidity are closely linked to cancer status, yet most studies only use duration since cancer diagnosis as a severity marker. The aim of the study was to validate a new pragmatic definition. Methods: Medical journals of 600 patients, with breast-, lung- and colorectal cancer from the Department of Oncology at Herlev-Gentofte Hospital were retrospectively reviewed. We defined active cancer as a cancer diagnosis, not followed by a potentially curative procedure within 6 months of the diagnosis. The remaining patients were characterized as having non-active cancer. This dichotomization was then compared to a cancer status assessment based on treatment received and paraclinical test such as their first post-procedural control scan. Based on this comparison, we calculated the positive predictive value (PPV) of our definitions of active and non-active cancer. Results: The calculated PPVs for active breast-, lung- and colorectal cancer were 87% (CI 95%: 0.74-0.99), 91% (CI 95%: 0.87-0.96) and 82% (CI 95%: 0.73-0.91). The PPVs for non-active breast-, lung- and colorectal cancer were 95% (CI 95%: 0.92-0.99), 91% (CI 95%: 0.82-0.99) and 73% (CI 95%: 0.66-0.81), respectively. Conclusion: We found an overall high PPV for both active and non-active cancer across all three types of cancer. Keywords: active cancer, non-active cancer, DNPR, validation, epidemiology

The Danish National Patient Registry (DNPR) provides unique epidemiological insight, but often lacks granular data. We propose a procedure-based definition of cancer status in patients with breast-, lung- and colorectal cancer, which can be applied to administrative health databases. New definitions of cancer status are needed as mortality and morbidity are closely linked to cancer status, yet most studies only use duration since cancer diagnosis as a severity marker. The aim of the study was to validate a new pragmatic definition. Medical journals of 600 patients, with breast-, lung- and colorectal cancer from the Department of Oncology at Herlev-Gentofte Hospital were retrospectively reviewed. We defined active cancer as a cancer diagnosis, not followed by a potentially curative procedure within 6 months of the diagnosis. The remaining patients were characterized as having non-active cancer. This dichotomization was then compared to a cancer status assessment based on treatment received and paraclinical test such as their first post-procedural control scan. Based on this comparison, we calculated the positive predictive value (PPV) of our definitions of active and non-active cancer. The calculated PPVs for active breast-, lung- and colorectal cancer were 87% (CI 95%: 0.74-0.99), 91% (CI 95%: 0.87-0.96) and 82% (CI 95%: 0.73-0.91). The PPVs for non-active breast-, lung- and colorectal cancer were 95% (CI 95%: 0.92-0.99), 91% (CI 95%: 0.82-0.99) and 73% (CI 95%: 0.66-0.81), respectively. We found an overall high PPV for both active and non-active cancer across all three types of cancer.